Professor Nick Thomson
Nicholas Thomson is Professor of Bacterial Genomics and Evolution in the department of Pathogen Molecular Biology, at LSHTM. He is also a Principal Scientist at the Wellcome Trust Sanger Institute within the Pathogen Genomics and Biology Program and holds an Honorary Chair at School of Medicine, University of St Andrews.
His research has focused on members of the Enterobacteriaceae including Vibrio cholerae, Salmonella sp & subsp, pathogenic E. coli, Shigella sp, Citrobacter and Yersinia. In addition, he also studied the genetic makeup and diversity of other non-enteric bacteria ranging from Chlamydia to Burkholderia. For Chlamydia his group led the work to produce the first reference genome sequence of a lymphogranuloma venereum (LGV) C. trachomatisisolate and has gone to show that the epidemic LGV isolates (LGV L2b) thought to represent a new more infectious form on LGV was in fact an old strain causing a new disease. Since this time his work has broadened to focus on understanding and defining the population structure of all three disease-causing variants of C. trachomatis. For along time it has been assumed that Chlamydia do not recombine. However, recent work by his group and collaborators has shown conclusively that the ompA gene used to subtype C. trachomatis isolates is a chimera formed by a ‘mix and match’ process of recombination. This work has also provided evidence of widespread DNA exchange throughout the genome between clinical isolates affecting different body sites and causing sexually transmitted or ocular infections, showing that C. trachomatis are able to recombine freely and that there are in fact few barriers to recombination. This fact alone challenges much of our understanding of the population structure of C. trachomatis. To facilitate this work his group has developed methods to sequence Chlamydia directly from uncultured discarded clinical swabs enabling his group to extend their population studies. This methodology has broad applications in clinical microbiology.
His research on Salmonella has focused on the diversity and genotypic differences between salmonellae with different host-ranges and disease outcomes. This has resulted in the generation of whole genome reference sequences for many of the major human and animal pathogenic serotypes of S. enterica. His early genomic research focused on patterns of evolution involving gene acquisition mediated by phage or other mobile genetic elements and identified serotype-specific genes that plot the evolutionary divergence both within the salmonellae as well as from broader members of the Enterobacteriaceae. However, it soon became clear from this work that gene loss was as important to pathogen evolution as gene gain with a clear association between host restriction in the salmonellae and concomitant functional gene loss.
In addition his group has contributed to a ‘One Health’ look at the flow of antimicrobial resistance and the zoonotic pathogen Salmonella Typhimurium DT104 (DT104) that carries these determinant by considering isolates from both humans and farm animals over the same 22-year period in Scotland. Contrary to popular belief this study showed that DT104 and antibiotic resistance genes found in it were largely maintained separately within the local animals (mainly cattle) and the human population, with only a small amount of spillover between the two hosts. It was also evident that the combination and array of resistance genes seen in humans was different to that found in local animals. He considers studies of this nature and resolution to be essential if we are to identify the sources and sinks of both food borne pathogens such as DT104 and AMR. AMR being considered by many as one of the most important threats to public health.
He has also worked to determine the phylogenetic makeup and contemporary and historical distribution of species within the genus Shigella and pandemic seven Vibrio cholerae. His work on cholera used modern techniques and genomic data to identify a global source for pandemic cholera. This work not only concentrates on determining their global distribution but also attempts to understand the drivers for this and the patterns of continued spread between countries and within communities. More recent work in this area has looked more deeply into plotting the national spread of V. cholerae clones, showing firstly that this can be done by genomic approaches with isolates separated by only a few weeks and that it can practical information that can be used to inform public health measures.
Current Research interests include linking phenotype to genotype: Using Phylogenomics of isolates competing within their natural host to identify novel and known factors associated with ‘fitness’ and onward transmission. Understanding how pathogen variation may impact on host-pathogen interactions and continuing to use genomics towards a better understanding of infectious disease and global health.